This application will allow the applicant to pursue a graduate research degree and contribute to the Nation's health sciences research agenda by investigating the role of exercise (mechanical loading) during growth on lifelong skeletal health. Exercise is a commonly advocated intervention for osteoporosis as the skeleton is mechanosensitive and can adapt to loading. However, a disparity exists between when the skeleton is responsive to exercise (pre-puberty) and when it is prone to osteoporotic fracture (adulthood). This has raised the question of whether exercise-induced bone changes during growth persist into adulthood where they would be most advantageous in reducing fracture risk. The sponsors'preliminary data indicate that loading-induced structural changes in cortical bone are maintained long-term and contribute to lifelong enhancement of bone strength. The current application will explore this further in three translational animal studies by investigating: (1) the short- and long-term preservation of loading benefits at both cortical and trabecular sites;(2) the influence of an artificial menopause (induced via ovariectomy) on the preservation of loading effects, and;(3) potential mechanisms for the maintenance or loss of loading-induced changes. In each study, bone adaptation will be induced in the right forelimb or hindlimb of young rats using the ulna or tibial axial loading models, respectively. Left limbs will serve as nonloaded, internal controls. Animals will subsequently be detrained (restricted to cage activities) for 12, 18 or 92 wks, with ovariectomy being performed in some animals to induce an artificial menopause. Bone response to loading and detraining will be assessed using a combination of in vivo and ex vivo analyses. To complement these animal studies, a fourth clinical study will be performed in which throwing athletes will be explored as a potential human model for the lifelong skeletal benefits of exercise during growth. This later study will provide preliminary data for future clinical studies on this topic. PUBLIC HEALTH RELEVANCE: A commonly prescribed treatment for the increased risk for osteoporotic fracture associated with aging is exercise. However, the skeleton is most responsive to exercise around the time of puberty, and not when it is prone to osteoporotic fracture in later adulthood. This has raised the question of whether exercise-induced bone changes during growth persist into adulthood where they would be most advantageous in reducing bone fracture risk. This application will investigate the role of exercise during growth on long-term skeletal health.